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Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury through an established rat model of corneal scarring. After induction of corneal scarring by irregular phototherapeutic keratectomy (irrPTK), MSC exosome preparations (MSC-exo) or PBS vehicle as controls were applied to the injured rat corneas for five days. The animals were assessed for corneal clarity using a validated slit-lamp haze grading score. Stromal haze intensity was quantified using in-vivo confocal microscopy imaging. Corneal vascularization, fibrosis, variations in macrophage phenotypes, and inflammatory cytokines were evaluated using immunohistochemistry techniques and enzyme-linked immunosorbent assays (ELISA) of the excised corneas. Compared to the PBS control group, MSC-exo treatment group had faster epithelial wound closure (0.041), lower corneal haze score (p = 0.002), and reduced haze intensity (p = 0.004) throughout the follow-up period. Attenuation of corneal vascularisation based on CD31 and LYVE-1 staining and reduced fibrosis as measured by fibronectin and collagen 3A1 staining was also observed in the MSC-exo group. MSC-exo treated corneas also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+, CD206+ M2 macrophages over CD80+, CD86+ M1 macrophages (p = 0.023), reduced levels of pro-inflammatory IL-1\u03b2, IL-8, and TNF-\u03b1, and increased levels of anti-inflammatory IL-10. In conclusion, topical MSC-exo could alleviate corneal insults by promoting wound closure and reducing scar development, possibly through anti-angiogenesis and immunomodulation towards a regenerative and anti-inflammatory phenotype.<\/jats:p>","DOI":"10.3390\/ijms24087456","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T01:39:05Z","timestamp":1681868345000},"page":"7456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5475-8712","authenticated-orcid":false,"given":"Hon Shing","family":"Ong","sequence":"first","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Corneal and External Diseases Department, Singapore National Eye Centre, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-0484","authenticated-orcid":false,"given":"Andri K.","family":"Riau","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8445-3669","authenticated-orcid":false,"given":"Gary Hin-Fai","family":"Yam","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Zahirah Binte M.","family":"Yusoff","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina J. Y.","family":"Han","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze-Wei","family":"Goh","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-8535","authenticated-orcid":false,"given":"Ruenn Chai","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology & Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Kiang","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology & Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6362-4898","authenticated-orcid":false,"given":"Jodhbir S.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Corneal and External Diseases Department, Singapore National Eye Centre, Singapore 168751, Singapore"},{"name":"School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1136\/postgradmedj-2015-133323","article-title":"Corneal infections in the 21st century","volume":"91","author":"Ong","year":"2015","journal-title":"Postgrad. Med. J."},{"key":"ref_2","first-page":"44","article-title":"Managing ocular surface disease: A common-sense approach","volume":"29","author":"Ong","year":"2016","journal-title":"Community Eye Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jtos.2019.10.010","article-title":"Validation of a clinical assessment tool for cicatrising conjunctivitis","volume":"18","author":"Ong","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Saccu, G., Menchise, V., Giordano, C., Delli Castelli, D., Dastru, W., Pellicano, R., Tolosano, E., Van Pham, P., Altruda, F., and Fagoonee, S. (2021). Regenerative Approaches and Future Trends for the Treatment of Corneal Burn Injuries. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020317"},{"key":"ref_5","unstructured":"EBAA (2020, October 10). Eye Banking Statistical Report. Available online: https:\/\/restoresight.org\/wp-content\/uploads\/2020\/04\/2019-EBAA-Stat-Report-FINAL.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1097\/TP.0b013e3181903b0a","article-title":"Risk factors for human corneal graft failure within the Australian corneal graft registry","volume":"86","author":"Williams","year":"2008","journal-title":"Transplantation"},{"key":"ref_7","first-page":"T10","article-title":"Development of Selective Lamellar Keratoplasty within an Asian Corneal Transplant Program: The Singapore Corneal Transplant Study (An American Ophthalmological Society Thesis)","volume":"113","author":"Tan","year":"2015","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1136\/bjophthalmol-2020-316149","article-title":"Evolution of therapies for the corneal endothelium: Past, present and future approaches","volume":"105","author":"Ong","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","article-title":"Global estimates of visual impairment: 2010","volume":"96","author":"Pascolini","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(12)60437-1","article-title":"Corneal transplantation","volume":"379","author":"Tan","year":"2012","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ophtha.2013.12.017","article-title":"A comparison of lamellar and penetrating keratoplasty outcomes: A registry study","volume":"121","author":"Coster","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1136\/bjophthalmol-2015-307427","article-title":"Aetiology-specific comparison of long-term outcome of deep anterior lamellar keratoplasty for corneal diseases","volume":"100","author":"Ogawa","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/jamaophthalmol.2015.4776","article-title":"Global Survey of Corneal Transplantation and Eye Banking","volume":"134","author":"Gain","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/ICO.0000000000002949","article-title":"The Impact of the COVID-19 Pandemic on Corneal Transplantation in Brazil","volume":"41","author":"Moriyama","year":"2022","journal-title":"Cornea"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.4103\/ijo.IJO_1740_21","article-title":"Year one of COVID-19 pandemic in India: Effect of lockdown and unlock on trends in keratoplasty at a tertiary eye centre","volume":"69","author":"Das","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_16","unstructured":"Australian Corneal Graft Registry, C (2019, May 09). The Australian Graft Registry 2018 Report. Available online: https:\/\/dspace.flinders.edu.au\/xmlui\/bitstream\/handle\/2328\/37917\/ACGR%202018%20Report.pdf?sequence=3&isAllowed=y."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ajo.2019.06.012","article-title":"Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty","volume":"207","author":"Woo","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.2217\/rme-2016-0054","article-title":"Advances in corneal cell therapy","volume":"11","author":"Fuest","year":"2016","journal-title":"Regen. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1167\/iovs.18-24428","article-title":"The Corneal Basement Membranes and Stromal Fibrosis","volume":"59","author":"Medeiros","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1167\/iovs.10-7066","article-title":"Ocular fibroblast diversity: Implications for inflammation and ocular wound healing","volume":"52","author":"Xi","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1167\/iovs.07-0972","article-title":"Cytokine, chemokine, and adhesion molecule expression mediated by MAPKs in human corneal fibroblasts exposed to poly(I:C)","volume":"49","author":"Liu","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/archopht.1982.01030030480022","article-title":"Production of first component of complement by corneal fibroblasts in tissue culture","volume":"100","author":"Mondino","year":"1982","journal-title":"Arch. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0014-4835(91)90241-6","article-title":"Cytokine regulation of C3 and C5 production by human corneal fibroblasts","volume":"53","author":"Rothman","year":"1991","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00281-008-0110-y","article-title":"The role of complement in ocular pathology","volume":"30","author":"Bora","year":"2008","journal-title":"Semin. Immunopathol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Kim, K.W., Joo, K., and Kim, J.C. (2016). Angiogenin ameliorates corneal opacity and neovascularization via regulating immune response in corneal fibroblasts. BMC Ophthalmol., 16.","DOI":"10.1186\/s12886-016-0235-z"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"620284","DOI":"10.3389\/fimmu.2021.620284","article-title":"Resident Innate Immune Cells in the Cornea","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/mi.2016.139","article-title":"CCR2(-) and CCR2(+) corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion","volume":"10","author":"Liu","year":"2017","journal-title":"Mucosal. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.biomaterials.2017.11.028","article-title":"MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity","volume":"156","author":"Zhang","year":"2018","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.gendis.2021.11.012","article-title":"Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing","volume":"9","author":"Chuah","year":"2021","journal-title":"Genes Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/S0140-6736(04)16104-7","article-title":"Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells","volume":"363","author":"Rasmusson","year":"2004","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/S0140-6736(08)60690-X","article-title":"Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study","volume":"371","year":"2008","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/scrt2","article-title":"Immunosuppression by mesenchymal stem cells: Mechanisms and clinical applications","volume":"1","author":"Ghannam","year":"2010","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1681\/ASN.2008070798","article-title":"Mesenchymal stem cell-derived microvesicles protect against acute tubular injury","volume":"20","author":"Bruno","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.scr.2009.12.003","article-title":"Exosome secreted by MSC reduces myocardial ischemia\/reperfusion injury","volume":"4","author":"Lai","year":"2010","journal-title":"Stem Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1440-1797.2012.01589.x","article-title":"Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model","volume":"17","author":"He","year":"2012","journal-title":"Nephrology (Carlton)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.5966\/sctm.2015-0078","article-title":"Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression","volume":"4","author":"Doeppner","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1089\/ten.tea.2017.0069","article-title":"Renal regenerative potential of different extracellular vesicle populations derived from bone marrow mesenchymal stromal cells","volume":"23","author":"Bruno","year":"2017","journal-title":"Tissue Eng. Part A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1609206","DOI":"10.1080\/20013078.2019.1609206","article-title":"Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications","volume":"8","author":"Witwer","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.semcdb.2015.03.001","article-title":"Mesenchymal stem cell exosomes","volume":"40","author":"Lai","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1042\/BST20180079","article-title":"MSC exosome works through a protein-based mechanism of action","volume":"46","author":"Toh","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1038\/s41598-017-04559-y","article-title":"Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis","volume":"7","author":"Bai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13287-022-02780-9","article-title":"Effect of small extracellular vesicles derived from IL-10-overexpressing mesenchymal stem cells on experimental autoimmune uveitis","volume":"13","author":"Li","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34562","DOI":"10.1038\/srep34562","article-title":"Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1","volume":"6","author":"Yu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1167\/iovs.18-25617","article-title":"Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1","volume":"60","author":"Zhang","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","first-page":"559","article-title":"Mesenchymal stem cells-derived exosomes ameliorate blue light stimulation in retinal pigment epithelium cells and retinal laser injury by VEGF-dependent mechanism","volume":"11","author":"He","year":"2018","journal-title":"Int. J. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"228","DOI":"10.4103\/1673-5374.226392","article-title":"Retinal ganglion cell neuroprotection by growth factors and exosomes: Lessons from mesenchymal stem cells","volume":"13","author":"Mead","year":"2018","journal-title":"Neural Regen Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jcyt.2021.01.001","article-title":"Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles","volume":"23","author":"Gimona","year":"2021","journal-title":"Cytotherapy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1479-5876-9-47","article-title":"Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs","volume":"9","author":"Chen","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tan, T.T., Lai, R.C., Padmanabhan, J., Sim, W.K., Choo, A.B.H., and Lim, S.K. (2021). Assessment of Tumorigenic Potential in Mesenchymal-Stem\/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV). Pharmaceuticals, 14.","DOI":"10.3390\/ph14040345"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"481","DOI":"10.2217\/rme.11.35","article-title":"Mesenchymal stem cell exosome: A novel stem cell-based therapy for cardiovascular disease","volume":"6","author":"Lai","year":"2011","journal-title":"Regen. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/scrt465","article-title":"Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models","volume":"5","author":"Tan","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1089\/scd.2013.0479","article-title":"Mesenchymal stem cells secrete immunologically active exosomes","volume":"23","author":"Zhang","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jcyt.2018.02.372","article-title":"Mesenchymal stromal cell exosome\u2013enhanced regulatory T-cell production through an antigen-presenting cell\u2013mediated pathway","volume":"20","author":"Zhang","year":"2018","journal-title":"Cytotherapy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.joca.2016.06.022","article-title":"Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration","volume":"24","author":"Zhang","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.arthro.2020.03.031","article-title":"Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model","volume":"36","author":"Wong","year":"2020","journal-title":"Arthroscopy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e13337","DOI":"10.1111\/acel.13337","article-title":"Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging","volume":"20","author":"Dorronsoro","year":"2021","journal-title":"Aging Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s13287-020-01887-1","article-title":"Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome","volume":"11","author":"Accarie","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, B., Lai, R.C., Sim, W.K., Choo, A.B.H., Lane, E.B., and Lim, S.K. (2021). Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020720"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chase, L.G., and Vemuri, M.C. (2012). Mesenchymal Stem Cell Therapy, Humana Press.","DOI":"10.1007\/978-1-62703-200-1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108062","DOI":"10.1016\/j.exer.2020.108062","article-title":"Keratocyte biology","volume":"196","author":"Yam","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1167\/iovs.04-0922","article-title":"Lipopolysaccharide-induced expression of intercellular adhesion molecule-1 and chemokines in cultured human corneal fibroblasts","volume":"46","author":"Kumagai","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.exer.2010.04.007","article-title":"Corneal myofibroblast generation from bone marrow-derived cells","volume":"91","author":"Barbosa","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/jnr.24067","article-title":"Sustained activation of ERK1\/2 MAPK in Schwann cells causes corneal neurofibroma","volume":"95","author":"Ishii","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_66","first-page":"2727","article-title":"Subepithelial corneal fibrosis partially due to epithelial-mesenchymal transition of ocular surface epithelium","volume":"16","author":"Kawashima","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3928\/1081597X-20190625-02","article-title":"Coordinated Modulation of Corneal Scarring by the Epithelial Basement Membrane and Descemet\u2019s Basement Membrane","volume":"35","author":"Wilson","year":"2019","journal-title":"J. Refract. Surg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.1167\/iovs.18-24803","article-title":"Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing","volume":"59","author":"Samaeekia","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"40548","DOI":"10.1038\/srep40548","article-title":"Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization","volume":"7","author":"Han","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2174\/1874364101509010049","article-title":"Ocular Surface as Barrier of Innate Immunity","volume":"9","author":"Navas","year":"2015","journal-title":"Open Ophthalmol. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.yjmcc.2009.12.021","article-title":"Derivation and characterization of human fetal MSCs: An alternative cell source for large-scale production of cardioprotective microparticles","volume":"48","author":"Lai","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1074\/mcp.M600393-MCP200","article-title":"Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells","volume":"6","author":"Sze","year":"2007","journal-title":"Mol. Cell Proteomics."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"714704","DOI":"10.1155\/2012\/714704","article-title":"IL-8 and MCP Gene Expression and Production by LPS-Stimulated Human Corneal Stromal Cells","volume":"2012","author":"Shtein","year":"2012","journal-title":"Int. J. Inflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.bbamcr.2013.02.030","article-title":"Molecular mechanism of transglutaminase-2 in corneal epithelial migration and adhesion","volume":"1833","author":"Tong","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chaurasia, S.S., Perera, P.R., Poh, R., Lim, R.R., Wong, T.T., and Mehta, J.S. (2013). Hevin plays a pivotal role in corneal wound healing. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081544"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1046\/j.1463-5224.2002.00243.x","article-title":"Veterinary ophthalmology in laboratory animal studies","volume":"5","author":"Munger","year":"2002","journal-title":"Vet. Ophthalmol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.1167\/iovs.17-23575","article-title":"Safety and Feasibility of Intrastromal Injection of Cultivated Human Corneal Stromal Keratocytes as Cell-Based Therapy for Corneal Opacities","volume":"59","author":"Yam","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7456\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:18:16Z","timestamp":1760123896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,18]]},"references-count":77,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087456"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087456","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,18]]}}}